Title

骨質疏鬆症病患使用alendronate及raloxifene與罹患食道疾病之相關性研究

Translated Titles

Association between alendronate v.s raloxifene and esophageal diseases among patients with osteoporosis

Authors

凃思嘉

Key Words

骨質疏鬆症 ; alendronate ; raloxifene ; 食道疾病 ; osteoporosis ; alendronate ; raloxifene ; esophageal diseases

PublicationName

中國醫藥大學醫務管理學系碩士班學位論文

Volume or Term/Year and Month of Publication

2012年

Academic Degree Category

碩士

Advisor

黃光華

Content Language

繁體中文

Chinese Abstract

目標:近年alendronate和raloxifene已成為骨質疏鬆症主要治療藥品,但文獻顯示兩者有不同程度之易造成食道急性傷害,而反覆的食道傷害可能造成相關食道疾病。本研究目的為探討服用alendronate與raloxifene罹患食道疾病之相關性。 方法:資料來源為2001至2010年「全民健康保險學術研究資料庫」之百萬承保抽樣歸人檔(LHID2005);研究對象為2002年至2009年個別單獨服用alendronate或raloxifene之女性病患,並排除第一次用藥前已診斷食道疾病者;排除2002年以前已服用者及2010年後才開始服用者。自研究對象首次服藥日追蹤至發生食道炎(ICD-9 code:530-530.19)、食道狹窄(530.3)、食道潰瘍(530.2)及食道回流(530.81)等食道疾病為止;以SAS 9.2版軟體進行統計,分析其影響因素。 結果:研究期間共有5,433位骨質疏鬆症患者,服用alendronate有3,661位,raloxifene有1,772位,罹患食道疾病者共829位(15.26%),其中食道炎666位(54.63%)為最多。影響因素方面,60歲以上(95%C.I.= 1.47-2.28)、累積劑量為中劑量(95% C.I.=1.12-1.64)、使用NSAIDs藥品(95%C.I.= 0.45-0.67)及罹患腸胃共病症者(95%C.I.= 0.12-0.23),有較高之相對危險性罹患食道疾病。 結論:使用兩種藥品與罹患食道疾病,均未達顯著差異,並以alendronate有較高之食道炎發生個案,研究結果發現年齡越高、累積中劑量、使用NSAIDs藥品及有腸胃共病症者,會顯著影響食道炎罹患。建議醫師處方兩種藥品時,針對高年齡患者、累積劑量高者,需持續做好用藥衛教,且有必要瞭解病患NSAIDs使用與腸胃共病症狀況,並需持續觀察服藥後食道疾病副作用發生與否,以提升用藥安全。 關鍵字:骨質疏鬆症、alendronate、raloxifene、食道疾病

English Abstract

Objective: Both alendronate and raloxifene have become the major treatment for osteoporosis in recent years. Nevertheless, the literatures show that both of them could result in acutely esophageal nociception in different degrees, and repeated esophageal nociception could cause relative esophageal diseases. This study therefore aims to discuss the correlations between taking alendronate and raloxifene and suffering from esophageal diseases. Method: Based on Longitudinal Health Insurance Database (LHID2005) in National Health Research Institutes within 2001-2010, female patients who took alendronate or raloxifene within 2002-2009 were selected as the research subjects. The patients who were diagnosed esophageal diseases before taking the medicine for the first time and the others who had taken the medicine before 2002 and after 2010 were excluded. The research subjects were traced from the first day of taking the medicine till the occurrence of esophageal diseases, such as esophagitis (ICD-9 code: 530-530.19), esophageal stenosis (530.3), esophageal ulcer (530.2), and esophageal reflux (530.81). SAS 9.2 was applied to analyzing the factors. Results: During the research period 3,661 within the 5,433 osteoporosis patients took alendronate and 1,772 took raloxifene. Total 829 patients (15.26%) suffered from esophageal diseases, in which 666 (54.63%) suffered from esophagitis. Regarding the factors, patients above the age of 60 (95% C.I.=1.47-2.28), with medium accumulated dose (95% C.I.=1.12-1.64), taking NSAIDs (95% C.I.=0.45-0.67), and suffering from gastrointestinal comorbidity (95%C.I.=0.12-0.23) appeared relatively higher risk on suffering from esophageal diseases. Conclusion: Taking such two types of medicine and suffering from esophageal diseases did not achieve significance; besides, alendronate appeared higher chance on esophagitis. The research outcomes discovered that patients with higher age, medium accumulated dose, NSAIDs, and gastrointestinal comorbidity were likely to affect the suffering from esophagitis. It is therefore suggested that when prescribing those two medicines, the doctors should continue health education to the aged patients and the ones with high accumulated dose, understand the usage of NSAIDs and the condition of gastrointestinal comorbidity of the patients, and constantly observe the side-effects of esophageal diseases after taking the medicine so as to promote the medication safety. Key words: osteoporosis, alendronate, raloxifene, esophageal diseases

Topic Category 醫藥衛生 > 醫院管理與醫事行政
公共衛生學院 > 醫務管理學系碩士班
社會科學 > 管理學
Reference
  1. 行政院衛生署國民健康局(2008):骨質疏鬆症學習手冊─更年期與骨質疏鬆。
    連結:
  2. 行政院衛生署國民健康局(2009):國民健康訪問暨藥品濫用調查。
    連結:
  3. 行政院衛生署國民健康局 (2011),骨質疏鬆症臨床治療指南。
    連結:
  4. 李瑋君、韓岳津、吳英黛等(2007),骨質疏鬆相關骨折住院病患之健保申報分析,
    連結:
  5. 施鈞偉(2008),都市化程度與居民健康:以台灣地區為例。成功大學公共衛生研究
    連結:
  6. 許志成、徐祥明、徐瑱淳等(2003),台灣地區老年人健康行為之影響因素分析,
    連結:
  7. 許月閔、張陽明、侯俊羽、張淑俐(2008),長期口服Bisphosphonates (Fosamax@)
    連結:
  8. 陳淑華、蔡來蔭、黃雅芬等(2006),參與社區篩檢婦女骨質疏鬆症威脅認
    連結:
  9. 陳美真、吳雅雯、顧宜瑾等(2006),台東地區老年人骨質疏鬆症之探討,台灣應
    連結:
  10. 陳冠宏(2010),台灣中老年人常見慢性病之症狀管理認知與因素探討。長榮大學
    連結:
  11. 楊再興、林瑞模、陳博光、黃國恩、楊榮森(2008)。中華民國骨質疏鬆症學會:
    連結:
  12. 黃建元、周川宏、邱千芳等(2006),南台灣成年人骨質疏鬆症之盛行率及相關危
    連結:
  13. 劉介宇、洪永泰、莊義利等(2006),台灣地區鄉鎮市區發展類型應用於大型健康
    連結:
  14. 張尹凡、蔡克嵩、陳依瀅等(2008),參與「臺灣骨鬆論壇」醫師對骨質疏鬆症防
    連結:
  15. 鄭丁元、溫啟邦、蔡孟娟等(2002),國人吸菸行為現況:2001年國民健康調查
    連結:
  16. 魏琦芳(2009),台灣地區成年人性別、教育、職業透過健康行為影響身體健康之
    連結:
  17. Audran M (2000). Raloxifene, selective estrogen receptor modulator (SERM)
    連結:
  18. Adami S, Pavelka K, Cline A, et al (2005). Upper gastrointestinal tract safety of daily
    連結:
  19. placebo-controlled trial. Mayo Clin Proc, 80(10):1278-1285.
    連結:
  20. Bredenoord J (2012). Mechanisms of Reflux Perception in Gastroesophageal Reflux
    連結:
  21. Disease: A Review. Am J Gastroenterol, 107:8–15.
    連結:
  22. alendronate 70 mg with concomitant non-steroidal anti-inflammatory drug use. Aliment Pharmacol Ther , 21(5): 599-607.
    連結:
  23. bisphosphonates in post-menopausal osteoporosis treatment in France. BMC Health Serv Res , 11(1): 151.
    連結:
  24. Chen TJ, Liu JY & Hwang SJ (2002). Non-steroidal anti-inflammatory drug and
    連結:
  25. Cardwell CR, Abnet CC, Cantwell et al (2010). Exposure to oral bisphosphonates and
    連結:
  26. risk of esophageal cancer. JAMA, 304(6):657-663.
    連結:
  27. Djulbegovic B, Wheatley K, Ross J, et al (2002). Bisphosphonates in multiple
    連結:
  28. myeloma. Cochrane Database Syst Rev, CD003188.
    連結:
  29. Enomoto S and Nakazawa K (2011). Steakhouse syndrome causing large
    連結:
  30. esophageal ulcer and stenosis. World J Gastrointest Endosc , 3(5): 101-104.
    連結:
  31. Indianapolis, IN.
    連結:
  32. Fujishiro H, Adachi K, Kawamura A, et al (2001). Influence of Helicobacter pylori
    連結:
  33. infection on the prevalence of reflux esophagitis in Japanese patients.
    連結:
  34. J Gastroenterol Hepatol, 16:1217–1221.
    連結:
  35. Food and Drug Administration (2007). Bisphosphonates and Alendronate Safety
    連結:
  36. Food and Drug Administration (2008). Bisphosphonates and Alendronate Safety
    連結:
  37. Gluer CC (2000). The use of bone densitometry in clinical practices. Bailliere’s
    連結:
  38. clinical Endocrinology and Metabolism, 14: 195-211.
    連結:
  39. Green J, G. Czanner, et al (2010). Oral bisphosphonates and risk of cancer of
    連結:
  40. oesophagus, stomach, and colorectum: case-control analysis within a UK primary care cohort. BMJ , 341(sep01 3): c4444-c4444.
    連結:
  41. Groen PC, Lubbe DF, Hirsch LJ, et al (1996). Esophagitis associated with the use of
    連結:
  42. alendronate. N Engl J Med, 335:1016-21.
    連結:
  43. alendronate in patients with osteoporosis: a randomized, double-blind, placebo-controlled study. Mayo Clin Proc, 77:1044-52.
    連結:
  44. Gennari C and Camporeale A (1997). Calcitonin in the treatment of osteoporosis.
    連結:
  45. Higuchi T and Mizunuma H (2004). Effects of SERM on breast cancer and
    連結:
  46. International Osteoporosis Foundation. About Osteoporosis fact sheet (2011).
    連結:
  47. Kikendall JW, Pill J and Cill K (2008) Clin. Esophagitis and Gastroenterol,
    連結:
  48. bisphosphonates for osteoporosis. ust Dent , 53(4): 354-357; quiz 366.
    連結:
  49. drugs:use and co-treatment with potentially interacting medications in the
    連結:
  50. elderly. Eur J Clin Pharmacol, 66:823–829.
    連結:
  51. the maxilla associated with oral bisphosphonate treatment. J Am Dent Assoc 138,1218-1220.
    連結:
  52. andgastroduodenal effects of risedronate and alendronate in postmenopausal women.Gastroenterology, 119:631-638.
    連結:
  53. Lichtenstein DR, Syngal S and Wolfe MM (1995). Nonsteroidal antiinflammatory
    連結:
  54. drugs and the gastrointestinal tract. The double-edged sword. Arthritis Rheum, 38: 5–18.
    連結:
  55. Liberman UA and Hirsch MD (1996). Esophagitis and alendronate. The New England
    連結:
  56. Lim LG and Ho KY (2003). Gastroespphageal reflux disease at the turn of
    連結:
  57. millennium.World J Gastroenterol, 9:2135-2136.
    連結:
  58. reflux disease. Am J Gastroenterol, 92:37-41.
    連結:
  59. effectiveness of treatments to prevent fractures in men and women with low bone density or osteoporosis. Ann Intern Med , 148:197-213.
    連結:
  60. Mariotti A (2008). Bisphosphonates and osteonecrosis of the jaws. J Dent Educ 72,
    連結:
  61. Nguyen DM, Schwartz J, Richardson P, et al (2010). Oral bisphosphonate
    連結:
  62. prescriptions and the risk of esophageal adenocarcinoma in patients with Barrett’s esophagus. Dig Dis Sci , published online 16 April.
    連結:
  63. National Institutes of Health (NIH). (2000). NIH consensus development conference
    連結:
  64. statement: osteoporosis prevention, diagnosis, and therapy, 27-29.
    連結:
  65. Naylor G and Davies MH (1996). Oesophageal stricture associated with alendronic
    連結:
  66. acid. The lancet, 348, 1030-1031.
    連結:
  67. Polisson R (1996). Nonsteroidal anti-inflammatory drugs: practical and theoretical
    連結:
  68. Paul and Seetharaman (2011). Esophageal stricture associated with alendronate use.
    連結:
  69. Canadian Medical Association Journal, 183(7), E429
    連結:
  70. Papapoulos (2011). Use of bisphosphonates in the management of postmenopausal
    連結:
  71. of action of bisphosphonates. Cancer, 88:2961-78.
    連結:
  72. Ross CE & Wu CL (1995). The links between education and health. American
    連結:
  73. Sociological Review, 60(5):719-745.
    連結:
  74. bisphosphonates in metastatic disease. Health Technol, 8:1-176.
    連結:
  75. plus progestin in healthy postmenopausal women: principalresults from the Women's Health Initiative (WHI) randomized controlled trial. JAMA, 288(3):321-33.
    連結:
  76. Ramsay SE, Morris RW, Lennon LT, et al(2008). Are social inequalities in mortality
    連結:
  77. in Britain narrowing? Time trends from 1978 to 2005 in a population-based study of older men. Journal of Epidemiology and Community Health, 62(1):75-80.
    連結:
  78. bisphosphonate medication adherence in a large longitudinal cohort of
    連結:
  79. women. Mayo Clin Proc, 80(7):856-861.
    連結:
  80. fractures in the elderly population of Taiwan. Bone, 44:125.
    連結:
  81. Stepan JJ (2002). Techniques for measuring bone mineral density. International
    連結:
  82. low-dose aspirin and its prevention by rabeprazole. J Clin Pharmacol, 50(3):320-30.
    連結:
  83. Taggart H, Bolognese MA, Lindsay R, et al (2002). Upper gastrointestinal tract safety
    連結:
  84. of risedronate: a pooled analysis of 9 clinical trials. Mayo Clin Proc,
    連結:
  85. Towner S and Burton DS (2011). Bisphosphonates for osteoporosis. N Engl J Med,
    連結:
  86. 364(6): 583; author reply 583-584.
    連結:
  87. Therapeutic Goods Administration (2007) Bisphosphonate Safety information
    連結:
  88. Usher C, Teeling M, Bennett K, et al (2006). Effect of clinical trial publicity on HRT
    連結:
  89. prescribing in Ireland. Eur J Clin Pharmacol, 62(4):307-310.
    連結:
  90. Initiative on osteoporosis therapy and expenditure in Medicaid. J Bone Miner Res , 21(5):765-771.
    連結:
  91. Vis M and Dijkmans BA (2011). Bisphosphonates for osteoporosis. N Engl J
    連結:
  92. before and during treatment of osteoporosis. Calcif Tissue Int , 86;110-5.
    連結:
  93. Watts NB and Diab DL (2010). "Long-term use of bisphosphonates in
    連結:
  94. osteoporosis." J Clin Endocrinol Metab 95(4): 1555-1565.
    連結:
  95. Wysowski DK (2009). Reports of esophageal cancer with oral bisphosphonate use.
    連結:
  96. N Engl JMed;360:89-90.
    連結:
  97. Wolfe MM, Lichtenstein DR and Singh G. (1999). Gastrointestinal toxicity of
    連結:
  98. onsteroidal anti-inflammatory drugs. N Engl J Med, 340:1888–99.
    連結:
  99. Yan Y, Wang W, Zhu H, et al (2009). The efficacy and tolerability of once-weekly
    連結:
  100. alendronate 70 mg on bone mineral density and bone turnover markers in postmenopausal Chinese women with osteoporosis. J Bone Miner Me tab 27, 471-478.
    連結:
  101. Zografos GN, Georgiadou D, Thomas D, et al. (2009). Drug-induced esophagitis.
    連結:
  102. Dis Esophagus , 22(8): 633-637.
    連結:
  103. Zahrowski JJ(2007). Bisphosphonate treatment :An orthodontic concem caIling for a
    連結:
  104. proactive approach. Am J Orthod Dentofacia1 Orthop ,131:311-320.
    連結:
  105. 參考文獻
  106. 中文文獻
  107. 行政院內政部統計處(2011):重要參考指標。
  108. http://sowf.moi.gov.tw/stat/indices/list.xls Accessed 06/30, 2011.
  109. http://www.bhp.doh.gov.tw/BHPnet/Portal/Them_Show.aspx?Subject=200712250018&Class=2&No=200712250099 Accessed 05/13, 2011.
  110. http://health99.doh.gov.tw/EducZone/edu_detail.aspx?CatId=21709 Accessed 05/13, 2012.
  111. 行政院衛生署中央健康保險局(2011):2003-2009年度藥品申報金額成長率分析。
  112. http://www.nhi.gov.tw/search/search.aspx Accessed 06/06, 2011.
  113. 行政院衛生署中央健康保險局(2011):全民健康保險藥品給付規定-第五章 激素
  114. 及影響內分泌機轉藥品。http://www.nhi.gov.tw/webdata/webdata.aspx?menu=20&menu_id=710&WD_ID=812&webdata_id=2919 Accessed 05/16, 2011.
  115. 行政院藥品資訊網(2011)。
  116. http://drug.doh.gov.tw/bulletin_cnt Accessed 05/16, 2011.
  117. 王慧瑜 (2009),骨質疏鬆症藥品之滿意度分析─以雲林縣某區域教學醫院為
  118. 例。雲林科技大學健康產業管理研究所碩士未出版論文。
  119. 李正?? (2008),漫談雙磷酸鹽業頁藥品相關額骨壞死。景福醫訊。12:2-9。
  120. 台灣醫學。11,22-8。
  121. 所未出版碩士論文。
  122. 台灣公共衛生雜誌。22(6),441-452。
  123. 許銘偉、林逸祥(2008):雙磷酸鹽類藥品(Bisphosphonates)之發展現況。
  124. http://www2.cch.org.tw/tumor/drug/drug20.html. Accessed 06/15, 2011.
  125. 藥品引起齒槽骨壞死一病例報告,臺灣口腔額面外科學會雜誌。19(2):91-99。
  126. 知之探討,志在護理。4(7),80-87。
  127. 用輻射與同位素雜誌。2(4),233-236。
  128. 醫務管理研究所未出版碩士論文。
  129. 骨質疏鬆症防治指引。http://www.bonecare.com.tw/toa/g.html Accessed 6/28, 2011.
  130. 險因子之研究,中華職業醫學雜誌。13(2),71-80。
  131. 調查抽樣設計之研究,健康管理學刊。4(1),1-22。
  132. 治之認知,台灣老年醫學暨老年學雜誌。3(2),120-129。
  133. 之分析,臺灣公共衛生雜誌。22(6),453-464。
  134. 徑路分析,護理暨健康照護研究。5(3),231-241。
  135. 英文文獻
  136. Introduction and conclusion. Joint Bone Spine , 67 Suppl 1: 3s-6s, 23s-25s.
  137. oral risedronate in patients taking NSAIDs a randomized, double-blind,
  138. Berry SD, Samelson EJ, Hannan MT, et al (2007).Second hip fracture in older men
  139. and women: The Framingham Study. Arch Intern Med, 167(18):1971-1976.
  140. Cryer B, Miller P, et al (2005). Upper gastrointestinal tolerability of once weekly
  141. Cotte FE and Pouvourville GDe (2011). Cost of non-persistence with oral
  142. antacid co-prescription in Taiwan: analysis of national insurance claims. Chinese Medical Journal, 65:588-93.
  143. Solomon DH, Daniel EF & Paul LR (2010).NSAIDs:Therapeutic use
  144. and variability of response in adults.
  145. Eli Lilly and Company Product Information: Forteo??(2004). teriparatide.,
  146. Eastell R & Ebeling PR (2009). Bone turnover markers: a key tool for
  147. understanding osteoporosis. Osteoporos Int , 20 Suppl 3, S237-238.
  148. Information.http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAler
  149. tsforHumanMedicalProducts/ucm150837.htm Accessed 06/06, 2011.
  150. Information. http://www.fda.gov/ohrms/dockets/ac/04/slides/2004-4067s 1_07 _Sachs%202%20Final. pdf-ll-l 0-2004. Accessed 09/08, 2011.
  151. Greenspan S, Field-Munves E, Tonino R, et al (2002). Tolerability of once-weekly
  152. Osteoporos Int, 7(Suppl 3):S159-S162.
  153. cardiovascular disease: making a comparison between raloxifene use and hormone replacement therapy on the risks of the diseases. Clin Calcium , 14(10): 81-84.
  154. http://www.iofbonehealth.org/patients-public/about-osteoporosis/what-is-osteoporosis.html. Accessed 05/13, 2011.
  155. 28:298-305.
  156. Kunchur R and Goss AN (2008). The oral health status of patients on oral
  157. Kathrine F, Vandraas, Olav Spigset, et al (2010). Non-steroidal anti-inflammatory
  158. Levin L, Laviv A and Schwartz-Arad D (2007). Denture-related osteonecrosis of
  159. Lanza FL, Hunt RH, Thomson AB, et al (2000). Endoscopic comparison if esophageal
  160. Journal of Medicine, 335(14):1069-1070.
  161. Lsolauri J, Luostarinen M, Lsolauri E, et al (1997). Natural course of gastroesphageal
  162. MacLean C, Newberry S, Maglione M, et al (2008). Systematic review: comparative
  163. 919-929.
  164. Miguel Angel Aibar-Arregui, Begona de-Escalante-Yanguela, Maria
  165. Munoz-Villalengua, et al (2011). Esophageal stenosis caused by alendronate. Revista espanola de enfermedades digestives, 103(3), 38-339.
  166. Ohta H (2006). Effect of raloxifene as a SERM on bone metabolism. Nippon
  167. Rinsho, 64(4):441-448.
  168. considerations in their selection. Am J Med, 100: 31S–6S.
  169. osteoporosis. New York Academy of Sciences, 1218:15–32.
  170. Rogers MJ, Gordon S, Benford HL, et al (2000). Cellular and molecular mechanisms
  171. Ross JR, Saunders Y, Edmonds PM, et al (2004). A systematic review of the role of
  172. Rossouw JE, Anderson GL, Prentice RL, et al (2002). Risks and benefits of estrogen
  173. Recker RR, Gallagher R & Maccosbe PE (2005). Effect of dosing frequency on
  174. Sato M, Turner CH, Wang T, et al (1998). A novel raloxifene analog with lmproved
  175. SERM potency and efficacy in vivo. The Journal of Pharmacology and Experimental Therapeutics, 287(1):1-7.
  176. Shao CJ, Hsieh YH, Tsai CH, et al (2009). A nationwide seven-year trend of hip
  177. Stafford RS, Drieling RL, Hersh AL (2004). National Trends in Osteoporosis Visits
  178. and Osteoporosis Treatment, 1988-2003. Arch Intern Med, 164:1525-30.
  179. Congress Series, 1229:63-68.
  180. Sweet MG, Sweet JM, Jeremiah MP, et al (2009). Diagnosis and treatment of
  181. osteoporosis. American Family Physician, Vol. 79 No.3.
  182. Sugimoto M, Nishino M, Kodaira C, et al (2010). Esophageal mucosal injury with
  183. 77:262-70.
  184. http://tga.gov.au/safety/2007/information-medicines.htm.
  185. Udell JA, Fischer MA, Brookhart MA, et al (2006). Effect of the Women’s Health
  186. Uetake T and Enomoto N (2007). Osteoporosis in elderly patients. Nihon Rinsho,
  187. 65(5):933-8.
  188. U.S.ankarca (2005).Gastrontestinal effects of sleletive and non-selective non-sterodial
  189. anti-inflammatoty drugs. Current Pharmacetuial Design, 11:1779-1793.
  190. Med ,364(6): 582-583; author reply 583-584.
  191. Valean S, Petrescu M & Pill Rom (2005). Micromedx healthcare
  192. Series –drug-induced esophagitis. Gastroenterol, 14(2):159-63.
  193. Vestergaard P, Schwartz K, Pinholt EM, et al (2010). Gastric and esophagus events
  194. WHO Study Group. (1994). Assessment of fracture risk and its application to
  195. screening for postmenopausal osteoporosis: Report of a WHO Study Group. WHO Technical Report Series, 843.